The long range goals of my research are: (1) to evaluate the effect of insulin resistance and altered glucose metabolism during pregnancy on fetal growth and development; (2) to develop clinical methodologies to diagnose women with gestational diabetes earlier in gestation; and (3) to test the value of treatment regimens based on the specific underlying metabolic abnormalities. The specific aims of this research proposal are: (1) to serially evaluate glucose metabolism and insulin resistance before and during pregnancy in lean and obese non-diabetic women; (2) to serially evaluate glucose metabolism and insulin resistance before and during pregnancy in lean and obese gestational diabetics matched for percent body fat, diet, age, parity and level of physical activity. We plan to achieve these initial specific aims by evaluating longitudinally 15 normal women matched with 15 gestational diabetics prior to conception and during early and late gestation. All subject will be evaluated using: (1) the oral glucose tolerance test; (2) the intravenous glucose tolerance test; (3) underwater weighing; (4) islet cell antibodies; and, (5) the hyperinsulinemic-euglycemic clamp with simultaneous indirect calorimetry. The specific methodology employed will allow evaluation of: (1) endogenous glucose production in the basal state and in response to insulin by the infusion of dideuterated glucose as the tracer during the "clamp"; (2) peripheral insulin resistance; (3) the route of glucose disposal whether by oxidative or non-oxidative routes; (4) insulin clearance; (5) glucose disappearance (K value) and 1st and 2nd phase insulin response; (6) the percent body fat; and (7) those women at risk for type 1 diabetes. These studies will resolve controversies in our understanding of insulin resistance and maternal glucose metabolism during gestation in normal and gestational diabetic women. The information obtained from these studies will provide us with the data to develop clinical methodologies to diagnose gestational diabetes earlier in gestation. We then plan to test the value of improved treatment regimens based on the specific metabolic abnormality, to decrease maternal and perinatal morbidity.